The generation of commodity chemicals from renewable feedstocks remains as one of the top priorities in the field of green chemistry. In addition, chemical processes that can operate in a catalytic fashion, such that toxic stoichiometric by-products can be avoided, will be essential in developing long-term, sustainable routes for molecules of interest. Though most catalytic processes in use today are mediated through the action of transition metals, recent advances have shown that certain all-organic scaffolds, i.e. containing only non-metal atoms such as carbon, hydrogen, nitrogen, sulfur, oxygen, or phosphorus, can act in a catalytic fashion and affect seemingly non-obvious transformations on reactive substrates.
One such scaffold that is capable of unusual transformations comprise heterocyclic rings in which three consecutive atoms in the ring are of the form ‘X+═C−—X’, with ‘X’ being nitrogen, sulfur, silicon, or phosphorus (FIG. 2). Upon treatment with a suitable base, these molecules generate stabilized, singlet carbenes, containing a divalent carbon center. These carbenes are capable of imparting very unusual reactivity on certain organic functional groups; the most well understood being that of the vitamin Thiamine on pyruvate during metabolism. Much of the current academic research on these carbenes focuses on the grouping ‘R(R′)N+═C—−XR″’, which have been termed ‘N-heterocyclic carbenes (NHC)’, and their action on aldehydes. Classically, aldehyde groups are considered to be highly reactive electrophiles, with a partial positive charge residing on the carbon atom. NHC organocatalysis is capable of reversing this charge, in a phenomenon known as ‘umpolong’ reactivity, wherein that same carbon now bears a partial negative charge in the aldehyde-NHC adduct (See Seebach Angewandte Chemie International Edition in English 18, 239 (1979)). The chemical literature contains examples of additions, eliminations, cycloadditions, and many other reactions where this intermediate is invoked.
Recent publications from Mark Mascal at the University of California, Davis, detailed a high yielding process from which 5-(chloromethyl)-2-furaldehyde (CMF) can be produced from a number of renewable cellulosic and hemicellulosic feedstocks (See Mascal and Nikitin Energy & Fuels 24, 2170 (2009)). As the process makes use of strong mineral acids, it is agnostic to stereochemistry and glycosidic linkages of the unit saccharides, and will convert six-carbon sugars to CMF, with the exception of deoxy sugars or gluconuric acids. Similar work in the field of furans-from-carbohydrates has focused on the generation of 5-(hydroxymethyl)-2-furaldehyde (HMF) (See Binder and Raines Energy & Environmental Science 3, 677 (2010)). Both CMF and HMF can be converted to valuable chemicals, primarily through catalytic hydrogenation to afford 5-methyl-2-furaldehyde or 2,5-dimethylfuran, or else oxidized to 2,5-furan-dicarboxylate, which can be used as a plastic monomer.
Of particular relevance to the present invention is the conversion of CMF to 5-(ethoxymethyl)-2-furaldehyde (EMF) by Mascal (See Nikitin and Mascal Angewandte Chemie International Edition 47, 47 (2008)), which has demonstrated favorable fuel characteristics in terms of its energy content (30.3 MJ L-1). Though similar to gasoline in this regard, EMF failed to blend with gasoline at an appreciable level, and is also prone to auto-oxidation upon extended standing by virtue of the reactive aldehyde group (FIG. 3).
α-chloro-aldehydes are substrates that have been studied by Bode, Rovis, and Scheidt with NHC catalysis (See Sohn and Bode Organic Letters 7, 3873 (2005)); Reynolds and Rovis Journal of the American Chemical Society 127, 16406 (2005)); Chan and Scheidt Organic Letters 7, 905 (2005)). Mechanistically, after addition of the carbene to the aldehyde, the negative charge at the aldehyde-carbon center will eliminate chloride, affording an enol intermediate (FIG. 4). After tautomerization to the ketone, exogenous nucleophiles, such as alcohols, water, or amines, will expel the azolium moiety and regenerate the catalytic cycle. The resultant acid, ester, or amide, respectively, is immune from further reaction with the catalyst. CMF can be considered as a α-chloro-aldehyde, however the carbon-chlorine σ-bond is separated from the aldehyde π-bond by the furan ring system. In functional groups wherein a π-bond or π-system connects certain atoms, the group can be considered as ‘vinylogous,’ ‘doubly-vinylogous,’ etc. For example, an amide functional group with a carbon-carbon double bond connecting the nitrogen to the carbonyl is called a ‘vinylogous amide.’ In the case of CMF, the carbon-chlorine group and the aldehyde are ‘doubly-vinylogous,’ or perhaps, ‘furanylogous,’ where the furan π-system connects the bonds, and thus preserves the reactivity.
The present invention describes the high yielding conversion of CMF and related derivatives of 5-methyl-2-furaldehyde to 5-methyl-2-furoic acid and derivatives thereof using this novel transformation, catalyzed by NHC molecules. CMF, which is produced from renewable carbohydrate feedstocks, can be converted to useful products in a catalytic manner, without using transition metals, pressurized hydrogen gas, or extremes of pressure or temperature.